Jean-Jacques Michels

Histologic Grade, But Not SYT-SSX Fusion Type, Is an Important Prognostic Factor in Patients With Synovial Sarcoma: A Multicenter, Retrospective Analysis

PURPOSE To assess the prognostic value of SYT-SSX fusion type, in comparison with other factors, in a population of 165 patients with synovial sarcoma (SS). PATIENTS AND METHODS Data on 165 patients with SS (141 with localized disease at diagnosis) were studied retrospectively. The following parameters were examined for their potential prognostic value: age at diagnosis, sex, tumor site (extremities v proximal/truncal), size, histology, mitotic count, necrosis, histologic grade (Federation Nationale des Centres de Lutte Contre le Cancer system), stage (1997 tumor-node-metastasis system classification), surgical margin status (assessed histologically), and fusion type (SYT-SSX1 v SYT-SSX2). Median follow-up time was 37 months (range, 2 to 302 months). RESULTS Among those patients with localized disease at diagnosis, median and 5-year disease-specific survivals (DSS) for the SYT-SSX1 and SYT-SSX2 subgroups were 126 months and 67.4% versus 82 months and 63.2%, respectively (P = .12). Median and 5-year metastasis-free survivals (MFS) were 84 months and 54.2% for SYT-SSX1 versus 50 months and 47.6% for SYT-SSX2 (P = .76). Univariate analyses showed that high histologic grade (grade 3), high mitotic count (>/= 10 mitoses/10 high-power fields), stage III disease, size greater than 7 cm, tumor necrosis, and presence of areas of poorly differentiated morphology were significant adverse prognostic factors for DSS and MFS, whereas SYT-SSX fusion type, tumor histology (biphasic v monophasic), and patient sex were not. Age greater than 35 years adversely affected DSS but not MFS. In multivariate analyses, histologic grade was the most significant prognostic factor for both DSS and MFS. CONCLUSION For patients with localized SS, histologic grade but not SYT-SSX fusion type is a strong predictor of survival.

Macroscopic lymph-node involvement and neck dissection predict lymph-node recurrence in papillary thyroid carcinoma.

OBJECTIVE Whether lymph-node dissection (LND) influences the lymph-node recurrence (LNR) risk in patients with papillary thyroid cancer remains controversial. The prognostic impact of macroscopic and microscopic lymph-node involvement at diagnosis is also an unresolved issue. A retrospective study was conducted to assess the influence of various LND procedures and to search for LNR risk factors. METHODS Overall 545 patients without distant metastases prior to surgery and main tumour > or =10 mm were included. A total thyroidectomy was performed in all patients with either no LND (Group 1, n=161), bilateral LND of the central and lateral compartments (Group 2, n=181) or all other dissection modalities (Group 3, n=203). Post-operative radioiodine was given to 496 (91%) patients. The 10-year cumulative probability of LNR was assessed and a prognostic study using multivariate analysis was performed. RESULTS Macroscopic lymph-node metastases were present in 118 patients, 57 diagnosed before surgery and 61 only at surgery (including 81% in the central compartment). Overall, the 10-year cumulative probability of LNR was 7%. Macroscopic lymph-node metastases (P=0.001), extra-thyroidal invasion (P=0.017) and male gender (P=0.05) were independent risk factors, while bilateral LND of the central and lateral compartments was protective (P=0.028). In patients with macroscopic lymph-node metastases, the 10-year probability was lower in Group 2 than in Group 3 (10% vs 30%, P<0.01). In patients without macroscopic lymph-node metastases (n=427), no significant differences were observed between the three LND groups. CONCLUSIONS Patients with macroscopic, but not microscopic, lymph-node involvement have a major LNR risk and need an optimal LND at primary surgery.

Trends in survival for patients with metastatic soft-tissue sarcoma†

The objective of this study was to determine whether the overall survival of patients with metastatic soft tissue sarcoma (STS) has improved over the last 20 years.

Human herpesvirus 8 immunostaining: A sensitive and specific method for diagnosing Kaposi sarcoma in paraffin-embedded sections

Human herpesvirus 8 (HHV-8) is recognized as a major causal agent of Kaposi sarcoma (KS), and it has been detected in all epidemiologic variants of KS. Until now, detection of HHV-8 in paraffin-embedded sections was done mostly by using reverse transcriptase–polymerase chain reaction. To assess the sensitivity and specificity of an anti–HHV-8 antibody and its potential usefulness for separating KS from its mimickers, we immunostained 72 KS samples and 108 samples of potential mimickers of KS with the monoclonal antibody latent nuclear antigen-1 (LNA-1; Advanced Biotechnologies, Columbia, MD). Cases of KS included all epidemiologic variants of the disease. Non-KS lesions included 34 angiosarcomas, 4 kaposiform hemangioendotheliomas, and 70 various benign vascular lesions. Immunostaining for CD31, CD34, and/or von Willebrand factor (factor VIII) also were performed in all cases. All but 1 case of KS (sensitivity, 99%) and none of the non-KS lesions (specificity, 100%) stained with the LNA-1 anti–HHV-8 antibody. The LNA-1 anti–HHV-8 antibody is a reliable marker of all variants of KS. Because KS mimickers are consistently negative for this marker, its use for diagnostic purposes is recommended.

Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database

BACKGROUND The predictive value of grade for benefit from adjuvant chemotherapy (AC) in soft tissue sarcoma (STS) patients has never been explored. PATIENTS AND METHODS From 1980 to 1999, 1513 adult patients with non-metastatic STS were included prospectively in the French Sarcoma Group database. Grade was assessed according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system after central review. RESULTS AC was delivered to 13 grade 1 patients (3%), 145 grade 2 patients (35%) and 262 grade 3 patients (62%). Young age, non-well-differentiated liposarcoma histology, deep location, bone and/or neurovascular invasion and grade 2 or 3 were significantly associated with a higher likelihood to receive AC. Median follow-up was 9 years. On multivariate analysis, AC was significantly associated with improved metastasis-free survival (MFS) [5-year MFS: 58% versus 49%, hazard ratio (HR) 0.7 (95% confidence interval (CI) 0.6-0.9), P = 0.01] and overall survival (OS) [5-year OS: 58% versus 45%, HR 0.6 (95% CI 0.5-0.8), P = 0.0002] in grade 3 patients. This was not observed in grade 2 patients [5-year MFS: 76% versus 73%, HR 0.8 (95% CI 0.5-1.2), P = 0.27; 5-year OS: 75% versus 65%, HR 0.8 (95% CI 0.6-1.1), P = 0.15]. CONCLUSION This large cohort-based analysis with long-term follow-up indicates that patients with FNCLCC grade 3 disease may benefit from AC.

Vascular proliferations of the skin after radiation therapy for breast cancer: clinicopathologic analysis of a series in favor of a benign process: a study from the French Sarcoma Group.

Cutaneous vascular proliferations that occur in the field of prior radiotherapy include angiosarcoma and small, cutaneous lesions with a pseudosarcomatous pattern that previously were reported as atypical vascular lesions or benign lymphangiomatous papules.

Risk of second primary cancer following differentiated thyroid cancer.

Concerns remain over the risk of cancer following differentiated thyroid carcinoma and its causes. Iodine-131 (131I) and external irradiation are known to have potential carcinogenic effects. Thyroid carcinoma is a polygenic disease which may be associated with other malignancies. We investigated the incidence of second cancer and its aetiology in a cohort of 875 patients (146 men, 729 women) with differentiated thyroid carcinoma originating from Basse-Normandie, France. Cancer incidence was compared with that of the general population of the Département du Calvados matched for age, gender and period. The cumulative proportion of second cancer was estimated using the life-table method. Factors that correlated with the risk of second cancer were studied using the Cox model. After a median follow-up of 8 years, 58 second cancers had been observed. Compared with general population incidence rates, there was an overall increased risk of second cancer in women [standardised incidence ratio (SIR)=1.52; P<0.01], but not in men (SIR=1.27; P>0.20). Increased risk related to cancers of the genitourinary tract (SIR=3.31; P<0.001), and particularly to cancer of the kidney (SIR=7.02; P<0.01). Multivariate analysis showed that age above 40 years (P<0.01) and a history of previous primary cancer (P<0.001) correlated with risk. In contrast, neither cervical irradiation nor cumulative activity of 131I was related to the risk. These data confirm that women with differentiated thyroid carcinoma are at risk of developing a second cancer of the genitourinary tract and kidney. Only age and medical history of primary cancer before thyroid carcinoma are risk factors for second cancer. Common environmental or genetic factors as well as long-term carcinogenic effects of primary cancer therapy should be considered.

Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group.

Clear cell sarcoma (CCS) is a rare tumor with a very poor prognosis that occurs predominantly in the distal extremities of young adults. Most patients bear the t(12;22) reciprocal translocation, which involves the EWS and ATF1 genes. The diagnosis of CCS usually is easy but may be challenging in unusual sites, and the detection of EWS‐ATF1 fusion transcripts is helpful to rule out a metastatic melanoma.

Proliferative activity in primary breast carcinomas is a salient prognostic factor

The goal of the current study was to investigate the prognostic impact of proliferative activity, together with the other classic clinicopathologic prognostic factors (tumor size, tumor grade, receptor status, ploidy, and lymph node status), in breast carcinoma by counting mitoses and evaluating S phase fraction (SPF) in fresh and frozen tumor samples.

Prognostic Factors and Impact of Adjuvant Treatments on Local and Metastatic Relapse of Soft-Tissue Sarcoma Patients in the Competing Risks Setting

In the medical literature many analyses of outcomes of sarcoma patients were performed without regard to the problem of “competing risks.”